Ann Thorac Surg 2001;72:939-942
© 2001 The Society of Thoracic Surgeons
Case report
Aggressive multimodal treatment of pleuropulmonary blastoma
Susan K. Parsons, MD, MRPa,b,g,
Steven J. Fishman, MDc,g,
Lidewij E. Hoorntje, MDa,
Diego Jaramillo, MDd,g,
Karen C. Marcus, MDe,g,
Antonio R. Perez-Atayde, MDf,g,
Harry P. Kozakewich, MDf,g,
Holcombe E. Grier, MDa,b,g,
Robert C. Shamberger, MDc,g
a Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
b Division of Hematology/Oncology, Children’s Hospital, Boston, Massachusetts, USA
c Department of Surgery, Children’s Hospital, Boston, Massachusetts, USA
d Department of Radiology, Children’s Hospital, Boston, Massachusetts, USA
e Department of Radiation Oncology, Children’s Hospital, Boston, Massachusetts, USA
f Department of Pathology, Children’s Hospital, Boston, Massachusetts, USA
g Harvard Medical School, Boston, Massachusetts, USA
Accepted for publication August 28, 2000.
Address reprint requests to Dr Parsons, Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115
e-mail: sparsons{at}partners.org
 |
Abstract
|
|---|
Pleuropulmonary blastoma is a rare intrathoracic neoplasm almost solely confined to childhood. Survival is poor. The authors report 2 children with extensive intrathoracic disease who are long term survivors after multimodal therapy. Both children received multiagent neoadjuvant chemotherapy, followed by surgical resection to remove all gross tumor. Postoperative chemotherapy was given to both children; radiotherapy was also given in the second case because of a question of positive tumor margins. Experience supports the use of multimodal therapy, including an aggressive surgical approach in the potentially curative treatment of this tumor.
|
Introduction
|
|---|
Primary malignancies of the lung are rare in children. Pleuropulmonary blastoma (PPB), an unusual primary intrathoracic neoplasm occurring almost exclusively in children, may originate from the lung itself, the pleura, and the mediastinum [1, 2]. Eighty percent of reported cases have been found in the right hemithorax [2]. An association with preexisting cystic lung disease also has been described [3, 4]. Children presenting with PPB usually have a recent history of a suspected respiratory infection refractory to antibiotics, associated with low-grade fever, dry cough, and less commonly, chest pain. The insidious presentation of this disease is in sharp contrast to the aggressive behavior of the tumor within and outside the thoracic cavity. Distant metastases have been reported to brain, bones, and abdominal viscera [1, 2, 5]. Surgical resection of the tumor offers best local control. If the site or extent of the tumor makes initial surgical resection impossible, neoadjuvant chemotherapy has been successful in reducing tumor bulk to allow definitive surgical resection [6]. Despite multimodal treatment with chemotherapy, radiotherapy, and surgery, survival is poor. We report the outcome of 2 children with nonmetastatic PPB who presented with extensive intrathoracic disease and are long-term survivors. They represent our clinic’s entire experience with this rare but devastating tumor over the past decade.
|
Case reports
|
|---|
Patient 1
The first patient presented in August 1990 at 3 and a half years of age with a 2-week history of persistent, wet cough, slightly increased respiratory rate and transient low-grade fever without associated exercise intolerance, shortness of breath, or nasal congestion. Initial evaluation was significant for markedly decreased breath sounds in the right lung fields, tachypnea to 40 breaths per minute, and a room air saturation of 98%. A chest radiograph revealed opacification of the right hemithorax (Fig 1). Follow-up computed tomography (CT) revealed a large heterogeneous mass with solid and cystic components without evidence of calcification (Fig 2). The mass of unclear origin occupied almost the entire right hemithorax producing mediastinal deviation to the left. The child underwent a thoracentesis of the cystic component of the mass, which was nondiagnostic. The oncofetal antigen screen was negative. The patient then underwent exploratory surgery of the right hemithorax through a right thoracotomy. The exploration revealed an unresectable mass with apparent extension into the mediastinum. Traction on the mass anteriorly or posteriorly would produce hypotension. The final pathology of the biopsy revealed pulmonary blastoma with a malignant cellular stroma having an embryonal-like pattern of growth. This blastematous tumor had areas of divergent differentiation including cartilagenous and rhabdomyoblastic components.
View larger version (146K):
[in this window]
[in a new window]
|
Fig 1. Anteroposterior radiograph of the chest reveals near complete opacification of the right hemithorax by a large mass, which displaces the mediastinum to the left. There is no evidence of rib involvement.
|
|
View larger version (116K):
[in this window]
[in a new window]
|
Fig 2. Contrast-enhanced computed tomography scan of the chest shows complete displacement of the hemithorax by a mass. The mass is predominantly cystic laterally but has a solid component medially (arrows). The heart is markedly displaced to the left.
|
|
A metastatic evaluation, consisting of a bone marrow aspirate and biopsy, and bone scan were negative. On the third postoperative day, the child began an individualized treatment regimen, consisting of cycles of vincristine, actinomycin-D, and cyclophosphamide, alternating with doxorubicin and cisplatin for 1 year, a treatment modeled after a case report by Ozkaynak and coworkers [7]. He received two cycles of each regimen with considerable radiographic decrease in the size of the mass (Fig 3). Moreover, the tumor appeared to be entirely within the right upper lobe without extension into the mediastinum. Three and a half months after his initial diagnosis, the patient underwent a right upper and middle lobectomy achieving complete resection of residual tumor. Intraoperatively, the mass was found to closely abut the pleura and to have cystic areas. Although there were numerous pleural adhesions, the tumor appeared to be completely resected. Examination of the tumor revealed a 9-cm hemorrhagic mass with solid and cystic components, weighing 193.5 g. The mass was largely necrotic with small regions of viable tumor and areas of cartilage. Microscopically, the tumor appeared better differentiated particularly in areas of rhabdomyoblastic differentiation and displayed more anaplasia and necrosis.
View larger version (132K):
[in this window]
[in a new window]
|
Fig 3. Coronal T1-weighted image of the chest after chemotherapy shows that most of the mass is of high signal intensity suggesting hemorrhage (arrow). The mediastinum has gone back to its normal position.
|
|
The role of radiotherapy in this case was debated extensively, although ultimately, the decision was made to offer only postoperative chemotherapy consisting of three more cycles of each regimen. At the completion of treatment in June 1991, the patient had received a total of 300 mg/m2 of doxorubicin. Follow-up CT of the chest revealed reexpansion of the right lower lobe and no evidence of residual disease.
In the 10 years since his initial diagnosis, the patient has remained free of disease. Pulmonary function remains stable at 75% to 80% of the predicted range, despite surgical removal of the right upper and middle lobes of the lung. Cardiac function also has remained normal. He enjoys a full range of physical activities and has had consistent linear growth and somatic development.
Patient 2
The second patient presented in July 1996 at 10 years of age with a 3-week history of dyspnea and cough, initially associated with low-grade fever that resolved. Two weeks before admission she had progressively worsening dyspnea; the cough became more pronounced both with exertion and at rest, particularly when she was reclining. The patient reported a 6-pound weight loss over the interval period, an intermittent burning sensation in the right chest, but no history of hemoptysis. Her initial physical examination revealed decreased breath sounds in the right chest. Her cardiac examination was remarkable for a grade III/VI holosystolic murmur and a hyperdynamic precordium. An echocardiogram revealed a small, membranous ventricular septal defect (VSD). An anteroposterior chest radiograph on the day of admission showed a very extensive mass occupying almost the entire right hemithorax (Fig 4). CT and MRI of the chest both revealed a large soft tissue mass in the right hemithorax, (Fig 5). The heart was displaced to the left; the mass impinged on the right and left atria. No chest wall invasion was appreciated. Percutaneous needle biopsies of the intrathoracic mass on two separate occasions showed a malignant tumor characterized by undifferentiated cells and rhabdomyoblasts indicating either rhabdomyosarcoma or some other tumor with rhabdomyosarcomatous differentiation. As classic diagnostic features for pulmonary blastoma were lacking, the patient underwent an open biopsy of several pleural/parenchymal nodules. Given the clinical setting, a diagnosis of pleuropulmonary blastoma seemed to be the most plausible diagnosis, although a primary rhabdomyosarcoma could not be entirely excluded.
View larger version (119K):
[in this window]
[in a new window]
|
Fig 4. Anteroposterior radiograph on the day of admission shows a very extensive mass occupying almost the entire right hemithorax. It is multilobulated and displaces the heart to the left.
|
|
View larger version (117K):
[in this window]
[in a new window]
|
Fig 5. Contrast-enhanced computed tomography scan of the chest shows a multilobulated mass. The central component of the mass is necrotic (arrow). It abuts the heart.
|
|
A metastatic evaluation, including bilateral bone marrow biopsies and bone scan, was negative. Given the tumor size and location, both surgery and radiation were not considered therapeutic options. The patient began a 1-year treatment with the same regimen as used for patient 1. MRI demonstrated an estimated 75% reduction in tumor volume after two cycles of each regimen with little further response to one additional cycle of each regimen. Although extensive, the lesion was confined to the right thoracic cavity. A right extrapleural pneumonectomy was performed as well as removal of the right hemidiaphragm. The peritoneum remained intact. The 355-g pneumonectomy specimen included the entire right lung, visceral pleura, parietal pleura, a small patch of pericardium, and the hemidiaphragm. The surgical margins did not contain tumor, although the orientation of the gross specimen was difficult at the inferior posteromedial region where it was resected off the inferior vena cava. Approximately 15% of the visceral pleura, and 2% to 5% of the parietal pleura, particularly the diaphragmatic surface, were occupied by nodules, the largest of which was a 3.0 x 4.0 x 6.0-cm mass between the lower lobe and the medial diaphragm and extending into the inferior pulmonary ligament. Tumor involved the lung parenchyma of all lobes as well as single hilar lymph node. The diaphragmatic muscle and inferior pulmonary ligament were invaded by tumor that possibly involved the surgical resection margins. The nondiaphragmatic parietal pleura was not penetrated by tumor and the pericardium, the bronchial, and vascular margins were not involved. Microscopically the tumor differed from the biopsies by displaying extensive rhabdomyoblastic differentiation.
Postoperatively, this patient underwent closure of the small membranous VSD with a Rashkind (clamshell) device and was started on digoxin. Approximately 3 weeks after the pneumonectomy, she resumed chemotherapy, completing her planned treatment by July 1997. The cumulative dose of doxorubicin was 300 mg/m2. In addition, she received radiation therapy to a portion of the right hemithorax to a total dose of 3,600 cGy, completing radiation therapy in March 1997. The decision to use radiotherapy in this case was based on the concern of residual disease, particularly at the inferior posteromedial, right hemithorax, where the pathologic margin was questioned.
In the 3 years she has been off treatment, she has had no evidence of local or distant disease. In contrast to the first patient, however, she does develop dyspnea on exertion with no evidence of cardiac dysfunction.
|
Comment
|
|---|
These cases represent two distinct surgical approaches to potentially curative resection of PPB. Neither tumor was resectable at presentation, based on tumor size and proximity to vital structures. Multiagent chemotherapy given as neoadjuvant treatment resulted in significant reduction of the tumor mass after two completed cycles. Subsequent radiographic imaging in patient 1 revealed that the tumor was located entirely in the upper and middle lobe of the right lung and a bilobectomy was performed; complete resection of residual tumor was achieved. In contrast, in patient 2, the original tumor was more extensive with involvement of the pleura and invasion of mediastinal structures. After chemotherapy, the tumor mass had decreased to a size that was confined solely to the right thoracic cavity. Given the extent of disease and its pleural involvement, the extrapleural pneumonectomy was chosen as the surgical approach. This technique, often used in the treatment of malignant pleural mesothelioma, involves removal of the entire lung and parietal pleura [8]. An extrapleural pneumonectomy was justified as the only residual disease was in the right chest and it appeared to be the only curative option. Both patients remain disease free at 10 and 3 years after initial diagnosis, respectively.
As is often the case, determination of the diagnosis of PPB was challenging in both patients. The differential diagnosis of intrathoracic masses is extensive and includes primary and metastatic tumors, lymphatic or vascular malformations, or both, or lung bud abnormalities [1, 2]. Tumors of chest wall origin include primitive neuroectodermal tumors/Ewing’s sarcoma or rhabdomyosarcoma. In both instances, surgical incisional biopsies were necessary to establish the diagnosis. Fine needle aspiration before the biopsy did not yield sufficient diagnostic information given the heterogeneous composition of the tumors.
In 1988, Manivel and associates [1] distinguished PPB as a separate diagnostic entity from pulmonary blastoma based on age at presentation and its histologic, biological, and clinical characteristics. PPB is confined to childhood whereas pulmonary blastoma occurs mostly in adults.
Although several of the previously reported cases have received multiagent chemotherapy, typically modeled after sarcoma treatment (eg, vincristine, actinomycin, cyclophosphamide) [7], the role of radiotherapy is more difficult to assess. Often, patients with great tumor bulk or with residual disease received radiotherapy with doses ranging from 4 to 55 Gy [1, 5–7]. In a metaanalysis of 50 patients, reported by Priest and colleagues [5], 16 children received radiation therapy, the majority of whom had purely solid tumors. Survival rates did not significantly differ among those treated with or without radiotherapy, although these data must be interpreted with caution.
The treatment algorithm employed for both of our patients consisted of multiagent neoadjuvant chemotherapy to shrink the tumor, followed by surgery to remove all gross disease. Postoperatively, both patients continued to receive chemotherapy to complete a 1-year treatment course. Radiotherapy was considered in both cases, but was administered only in the second patient because of concern about a resection margin being involved by tumor. During the 2 years off treatment, these children received radiologic imaging, initially with CT scans but later with chest radiographs every 3 to 6 months. They also received annual pulmonary function tests, particularly during periods of peak growth. Other screening included echocardiograms every 2 years and audiograms after each cycle containing cisplatin and at the end of therapy. The long-term follow-up of these children reveals distinct patterns of residual lung function predictable based on the extent of surgical resection and postoperative treatment. Specifically, the first patient enjoys near-normal lung function whereas the second patient, treated with right extrapleural pneumonectomy and radiotherapy, has only about 35% of the normal capacity with functional limitations. Neither patient has experienced delayed cardiac toxicity from doxorubicin or ototoxicity from cisplatin therapy. Our experience supports the use of multimodal therapy, as reported by others [7], including an aggressive surgical approach in the potentially curative treatment of PPB.
|
Acknowledgments
|
|---|
The authors gratefully acknowledge Dr Jorge Ortega’s assistance in the design of our first patient’s individualized treatment and his on-going interest in this case. We also thank the patients and their families for the privilege of participating in their care.
|
References
|
|---|
-
Manivel J.C., Priest J.R., Watterson J., et al. Pleuropulmonary blastoma: the so-called pulmonary blastoma of childhood. Cancer 1988;38:1516-1526.
-
Dehner L.P. Pleuropulmonary blastoma is the pulmonary blastoma of childhood. Semin Diagn Pathol 1994;11:144-151.[Medline]
-
Tagge E.P., Mulvihill D., Chandler J.C., et al. Childhood pleuropulmonary blastoma: caution against nonoperative management of congenital lung cysts. J Pediatr Surg 1996;31:187-190.[Medline]
-
Lopez-Andreu J.A., Ferris-Tortajada J., Gomez J. Pleuropulmonary blastoma and congenital cystic malformations. J Pediatr 1996;129:773-775.[Medline]
-
Priest J.R., McDermott M.B., Bhatia S., et al. Pleuropulmonary blastoma. A clinicopathologic study of 50 cases. Cancer 1997;80:147-161.[Medline]
-
Calabria R., Srikanth M.S., Chamberlin K., et al. Management of pulmonary blastoma in children. Am Surg 1993;59:192-196.[Medline]
-
Ozkaynak M.F., Ortega J.A., Laug W., et al. Role of chemotherapy in pediatric pulmonary blastoma. Med Pediatr Oncol 1990;18:53-56.[Medline]
-
Rusch V. Indications for pneumonectomy: extrapleural pneumonectomy. Chest Surg Clin N Am 1999;9:327-338.[Medline]
This article has been cited by other articles:
|
|
|
|
 
N. Girard, M. Barbareschi, J.-F. Cordier, and B. Murer
What is a rare tumour and how should it be dealt with clinically?
Pathology of the Lung,
June 30, 2010;
85 - 133.
[Abstract]
[Fulltext]
[PDF]
|
|
|
Top
Abstract
Introduction
